Cardiopulmonary arrest (CA) is a tragic event that is often associated with high mortality and poor quality of life outcome in all age groups. Children who survive CA commonly sustain neurological injury that potentially results in many years of dependency for all aspects of care. The pathophysiology and outcome of pediatric CA differs greatly between those that occur out-of-hospital (OH), commonly in healthy children, and those that occur in-hospital (IH), typically in children with complex underlying disorders. There is a great need for neuroprotec- tive therapies for both groups sustaining pediatric CA. Recently, landmark RCTs in adults with OH ventricular fibrillation or tachycardia associated CA and in newborns with birth associated hypoxic ischemic encephalopathy have demonstrated improved survival with good neurological outcome after therapeutic hypothermia (TH) when initiated within six hours of return of return of spontaneous circulation or birth. There are, however, major differ- ences in the etiology and pathophysiology of CA across age groups, and results in neonates and adults cannot be extrapolated to children. No RCT of TH has been performed in the pediatric (non-newborn) CA population. RCTs are now urgently needed to guide pediatric practice. Our investigative team has worked together since 2002 and has brought together two federally funded pediatric clinical research networks (PECARN and CPCCRN) to conduct the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) Trials. The primary objective of the THAPCA Trials will be to determine if TH improves survival with good neurobehavioral outcome in children who have been resuscitated after CA in the OH (THAPCA-OH Trial) and IH (THAPCA-IH Trial) settings. The Vineland Adaptive Behavior Scales will be used as the primary measure to assess neurobehavioral outcome in survivors. Secondary endpoints include survival at 12 months post CA, change in neurobehavioral function from pre-arrest baseline to the 12-month measurement, and neuropsychological and neurological abnormality scores at 12 months post CA. We will also determine the safety of TH by assessing all-cause 28-day mortality, incidence of infections, arrhythmias, and blood product administration within 7 days of CA. Finally, we will analyze surrogate indicators of brain injury including serum neuron specific enolase (NSE), magnetic resonance imaging (MRI), and electroencephalograms (EEG), and will collect DNA from subjects enrolled in the trials. DNA will be stored in a repository for future studies to identify genetic polymorphisms that may be associated with altered suscep- tibility to hypoxic-ischemic injury and/or responsiveness to therapeutic hypothermia. The THAPCA Trials will be seminal studies with important public health applicability in children. THAPCA will establish whether TH results in improved survival with good functional outcome in children who have sustained CA in the OH or IH setting. THAPCA is highly relevant to the mission of the NHLBI, and complements the NHLBI Resuscitation Outcomes Consortium (ROC). THAPCA will address critical gaps in knowledge by conducting the first major RCT related to CA in childhood. Cardiac arrest in children is a tragic event that often results in death or severe brain injury. The THAPCA Trials are studies that will determine whether whole body cooling of children who have had cardiac arrest will result in better survival and less brain injury.